A 12-year-old female with Noonan syndrome*

What causes Noonan syndrome?

Noonan syndrome is caused by mutations in genes associated with the RAS/MAPK cell-signalling pathway, which is required for normal cell division, proliferation, differentiation and migration. These mutations lead to loss of regulation of cell growth and division.

Mutations in the PTPN11 gene are implicated in > 50% of cases. Gene mutations in SOS1 are implicated in 10–15% and mutations in RAF1 and RIT1 account for approximately 5% each. A number of other genes account for the rest.

The genetic cause behind Noonan syndrome is unknown in up to 20% of cases.

What are the clinical features of Noonan syndrome?

Noonan syndrome affects males and females in all races. 50–70% of people with Noonan syndrome are of short stature. Weight and length at birth are usual normal, but growth slows over time. This is thought to be associated with abnormal levels of growth hormone.